RESUMEN
Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long noncoding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)18a5p in the promoter of CASC2. The level of miR18a5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR18a5p and inhibit miR18a5p expression, using reporter gene and RNA immunoprecipitation assays. miR18a5p suppressed CASC2 upregulationmediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR18a5p in the 3' untranslated region of Cterminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR18a5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the antimiR18a5pmediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR18a5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR18a5p. Our findings highlight the CASC2/miR18a5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC.
Asunto(s)
Proteínas Portadoras/genética , MicroARNs/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas Nucleares/genética , ARN Largo no Codificante/metabolismo , Proteínas Supresoras de Tumor/genética , Regiones no Traducidas 3'/genética , Adulto , Anciano , Apoptosis/genética , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Endodesoxirribonucleasas , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Nasofaringe/patología , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/genética , ARN Largo no Codificante/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
PURPOSE: We evaluated the risk of cochlear implantation through the round window membrane in the facial recess through a preoperative analysis of the angle between the facial nerve-round window and the cranial midline using high-resolution temporal bone CT. METHODS: Temporal bone CT films of 176 patients with profound sensorineural hearing loss at our hospital from 2013 to 2015 were reviewed. The preoperative temporal bone CT scans of the patients were retrospectively analysed. The vertical distance (d value) from the leading edge of the facial nerve to the posterior wall of the external auditory canal and the angle (α value) between the line from the leading edge of the facial nerve to the midpoint of the round window membrane and the median sagittal line on the round window membrane plane were measured. Based on intraoperative observation, the round window membrane was divided into complete round window membrane exposure (group A), partial exposure (group B), and unexposed (group C) groups, and statistical analysis was performed. RESULTS: The α value could be effectively measured for all 176 patients (62.60 ± 7.12), and the d value could be effectively measured for 95 cases (5.53 ± 1.00). An analysis of the correlation between the α and d values of these 95 cases found a negative correlation. Of the 176 cases, one-way analysis of variance (ANOVA) showed that the differences among the groups were significant [P = 0.000 (< 0.05)]. CONCLUSION: The angle (α value) between the line connecting the leading edge of the facial nerve to the midpoint of the round window and the median sagittal line measured in preoperative CT scans was associated with the difficulty of intraoperatively exposing the round window membrane. When the α value was larger than a certain degree, the difficulty of exposing the round window membrane was increased. In such cases, the surgeon should fully expose the round window membrane during surgery, which could result decrease the likelihood of complications.